In 1957, we initiated an experiment in which we selectively bred mice for a difference in leukocyte levels. In 1973, after 22 generations of selective breeding, we discovered the presence of amyloidosis in the strain selected for low leukocyte counts (LLC). The incidence of amyloidosis in LLC mice approaches 100 per cent in mice over one year of age. Therefore, amyloidosis in the LLC mice is an age dependent genetic disease. The proposed work represents an attempt to define the interaction between age and the gene or genes for the development of this disease in mice. We will determine through cross breeding, the mode of inheritance and whether the development of amyloidosis is controlled by a single recessive or a dominant gene. Previous studies indicate that amyloidosis can be adoptively transferred through spleen cell nuclei from casein treated mice. We will investigate whether such a factor is present in the LLC mice by transferring old LLC mouse spleen nuclei to genetic barriers by injecting old LLC spleen cell nuclei to C3H and similarly injecting casein treated C3H spleen nuclei to young LLC mice. Finally, we will determine the chemical nature of the transfer factor by injecting different nuclear fractions within and between the LLC and C3H strains. As a study of the intracellular origin of the amyloid protein, we will determine whether the rough endoplasmic reticulum is the site of its synthesis and the specific cell types involved. This attempt will be made through electron microscopy with peroxidase-anti-peroxidase staining procedures. The applicant hypothesizes that amyloidosis development results from reactivation of the structural gene or genes of amyloid protein which is depressed under ordinary circumstances. The proposed approaches represent primarily a search for evidence which may support his hypothesis and may explain the development of amyloidosis from a genetic perspective.